The meridian theory is the central theory of many complementary and alternative medicine (CAM) systems and it is the backbone of acupuncture and oriental medicine. The meridian theory deals with physiologic regulation and pathologic changes in the human body, and it guides the diagnosis and treatment of oriental medicine in many aspects, especially in relation to acupuncture. However, the biologic mechanisms of the meridian system and transduction of acupuncture signals on the meridian system remain unknown. Several reports have established the relevance of nitric oxide (NO), particularly the NO derived from endothelial nitric oxide synthase (eNOS) as a regulatory molecule in vascular tone, permeability, angiogenesis and tissue remodeling. We propose to investigate the CENTRAL HYPOTHESIS that acupuncture enhances the meridian communication system by activating nitric oxide synthase. We will use three different meridians: stomach meridian, liver meridian, large intestine meridian, to test our hypothesis. These meridians include three organs that are amenable to experiments by intravital microscopy and western blotting (cheek pouch in stomach meridian, cremaster in liver meridian, and mesentery in large intestine meridian). Our experiments will verify whether or not a) meridian acupoints can specifically stimulate changes in NOS expression or activation and NO production, and b) meridians are independent of each other or possess cross-talk capacity in stimulating NOS and NO production. Our focus is on understanding the normal state;however, because acupuncture assists in maintaining health, it may be difficult to detect its influence in healthy subjects. Therefore, we will use hypertension - a vascular disease state - to check whether or not salutary effects are induced by activation of acupoints along the meridians. We will apply methods of intravital microscopy, NO detection by NO-selective electrodes, and western blotting to examine the impact of acupuncture in the designed experiments. The following Specific Aims will test our central hypothesis in normal and disease states using hamsters. Aim 1: To determine whether or not stimulation of specific meridian acupoints induces production of NO. Aim 2: To assess whether acupuncture on a specific acupoint enhances the action of vasodilators through its specific meridian or several cross-talking meridians. AIM 3: To investigate the molecular mechanisms by which acupuncture regulates NOS activity along the meridians. Overall, the results should advance our understanding of the mechanisms of the meridian system and the new knowledge to be acquired by our research project may help to design new approaches to enhance the effectiveness of acupuncture treatments.